Journal
EXPERIMENTAL DERMATOLOGY
Volume 14, Issue 8, Pages 586-592Publisher
WILEY
DOI: 10.1111/j.0906-6705.2005.00329.x
Keywords
human; Th1/Th2 cells; autoimmunity; TCR; skin
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Pemphigus foliaceus (PF) is a severe autoimmune bullous disorder, characterized by autoantibodies (autoAb) against desmoglein 1 (Dsg1). As T cells may be critical in the pathology of PF, the aim of the present study was to identify and characterize autoaggressive T-helper cells reactive to Dsg1 in PF patients and healthy individuals. Eight patients with the clinical diagnosis of PF and six HLA class II-matched healthy individuals were examined. By magnetic cell-sorting (MACS) cytokine-secretion assay, Dsg1-responsive T-helper (Th) 1 and Th2 cells were isolated and cloned by limiting dilution. The generated T-cell clones (TCC) were characterized regarding proliferative response, TCR V beta-chain usage, and cytokine profile upon in vitro stimulation with Dsg1. Both Dsg1-reactive Th1 and Th2 cells were detected in PF patients and controls at similar frequencies. A total of 15 Th1 and Th2 clones were isolated from patients and 27 TCC from healthy controls. Analysis of TCR V beta-chain usage of autoreactive T cells from both groups revealed no predominance of a specific V beta chain. Noteworthy, the isolated TCC showed a polarized Th1- or Th2-like phenotype upon in vitro culture and stable expression of Th1 or Th2 cytokines during long-term in vitro culture. In summary, our data demonstrate that T-cell autoreactivity against Dsg1 is not restricted to patients with PF. Moreover, both Th1 and Th2 cells were present in patients and healthy donors, suggesting that the loss of B-cell tolerance against Dsg1 in PF is not exclusively determined by the presence of autoaggressive T cells.
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